Seven-membered heterocyclic rings represent an area of considerable interest mainly due to
its interesting pharmacological properties. Among them, undoubtedly, the [1]benzodiazepine
skeleton has been one of the most studied, and commonly associated with central nervous system
depressive effects. The [1] benzodiazepine framework is nowadays linked with antitumoral
activity, in such Fuligocandines A 1 and B 2 have been reported to display cytotoxic activity [1].

On the other hand, the hydroxypyrrolidine unit is the key building block for a variety of
derivatives that are known to play crucial roles in the functions of a number of anticancer,
antimicrobial and antiviral compounds among others. However, to the best of our knowledge,
there are no works reporting the synthesis of hydroxypyrrolidine rings fused to a [1]
benzodiazepine framework.
The synthesis of benzodiazepinones 6-8 has been accomplished according to the sequence
displayed on the scheme bellow. Catalyzed ionic liquid 5 equimolar reaction of hydroxyproline
3 with isatoic anhydride 4 afforded the corresponding benzodiazepine 6 in high yields (80%).
Subsequent hydroxy group transformation was efficiently accomplished using Ac2O and
diketene, obtaining the corresponding derivatives 7, 8 in good yields (70-80%).

References:
1. Pettersson B., Hasimbegovic V., Bergman J. Tetrahedron Lett. 2010, 51, 238.